Background Patients with severe Coronavirus Disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with acute respiratory distress syndrome (ARDS). It has been suggested that respiratory failure in COVID-19 represents a novel pathologic entity. Research Question How does the lung histopathology described in COVID-19 compare to the lung histopathology described in SARS and H1N1 influenza? Study Design and Methods: We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020 using search terms for COVID-19, H1N1 influenza and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-IPD guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. Results In COVID-19, acute phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared to 24% of H1N1 influenza patients. Interpretation DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared to H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.
As part of an effort to create a point-of-care diagnostic system for the developing world, we present a microfluidic flow-through membrane immunoassay with on-card dry reagent storage. By preserving reagent function, the storage and reconstitution of anhydrous reagents enables the devices to remain viable in challenging, unregulated environmental conditions. The assay takes place on a disposable laminate card containing both a porous membrane patterned with capture molecules and a fibrous pad containing an anhydrous analyte label. To conduct the assay, the card is placed in an external pumping and imaging instrument capable of delivering sample and rehydrated reagent to the assay membrane at controlled flow rates to generate quantitative results. Using the malarial antigen Plasmodium falciparum histidine-rich protein II (PfHRP2) as a model, we demonstrate selection of dry storage conditions, characterization of reagent rehydration, and execution of an automated on-card assay. Gold-antibody conjugates dried in a variety of sugar matrices were shown to retain 80-96% of their activity after 60 days of storage at elevated temperatures, and the release profile of the reconstituted reagent was characterized under flow in microfluidic channels. The system gave a detection limit in the sub-nanomolar range in under nine minutes, showing the potential to expand into quantitative, multi-analyte analysis of human blood samples.
BackgroundSpaced education is a novel method that improves medical education through online repetition of core principles often paired with multiple-choice questions. This model is a proven teaching tool for medical students, but its effect on resident learning is less established. We hypothesized that repetition of key clinical concepts in a “Clinical Pearls” format would improve knowledge retention in medical residents.MethodsThis study investigated spaced education with particular emphasis on using a novel, email-based reinforcement program, and a randomized, self-matched design, in which residents were quizzed on medical knowledge that was either reinforced or not with electronically-administered spaced education. Both reinforced and non-reinforced knowledge was later tested with four quizzes.ResultsOverall, respondents incorrectly answered 395 of 1008 questions (0.39; 95% CI, 0.36–0.42). Incorrect response rates varied by quiz (range 0.34–0.49; p = 0.02), but not significantly by post-graduate year (PGY1 0.44, PGY2 0.33, PGY3 0.38; p = 0.08). Although there was no evidence of benefit among residents (RR = 1.01; 95% CI, 0.83–1.22; p = 0.95), we observed a significantly lower risk of incorrect responses to reinforced material among interns (RR = 0.83, 95% CI, 0.70–0.99, p = 0.04).ConclusionsOverall, repetition of Clinical Pearls did not statistically improve test scores amongst junior and senior residents. However, among interns, repetition of the Clinical Pearls was associated with significantly higher test scores, perhaps reflecting their greater attendance at didactic sessions and engagement with Clinical Pearls. Although the study was limited by a low response rate, we employed test and control questions within the same quiz, limiting the potential for selection bias. Further work is needed to determine the optimal spacing and content load of Clinical Pearls to maximize retention amongst medical residents. This particular protocol of spaced education, however, was unique and readily reproducible suggesting its potential efficacy for intern education within a large residency program.
Immune checkpoint inhibitors are known to cause a variety of immune-related adverse events, including pneumonitis. When symptomatic, treatment typically consists of temporary or permanent cessation of the checkpoint inhibitor and several weeks of corticosteroid therapy. However, a subset of patients may suffer from severe pneumonitis, and the optimal treatment for this group is not known. Here we describe the case of a patient receiving pembrolizumab for non-small cell lung cancer who developed severe checkpoint inhibitor pneumonitis. After treatment with high-dose corticosteroids failed to produce a response, a course of intravenous immunoglobulin catalyzed rapid and durable improvement. In this review, we discuss the current evidence regarding the incidence and outcomes of severe checkpoint inhibitor pneumonitis and propose a role for intravenous immunoglobulin as a possible treatment strategy.
We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I–II study of clofarabine–melphalan–alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration–time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal.
Z w e i t e A b h a n d l u n g. (Eingelaufen den 15. October 1878.) L Weitere Beitrage zur Kennhifs der Fumarslime und Male'inskre; von Camille Petri Die Porineln, welche in der crsteri Abhandiung iiber diese Untersuchungen *) ffir die Constitutiori der Funiarsaure und Maleinsaure aufgestellt wurden, erklaren alle bisher beobachteten Thatsachen so vollstandig , M s diese als eine nobhwendige Folge einer derartigen Constitution erscheinen ; nur die Existenz von zwei unzweifelhaft von cinander verschiedeaen Monobrommaleinsaurerr %*) stehl damit in1 Widerspruch. *) Diem Annaleu XB8, 95. a*) Weno icb in der ersten Abbandlung von nur smei isomeren Brommaleiosluren sprach, 80 wat es mir WON bekannt, dak K e k n l 6 aufser der von ibm daqeetellten Bromund bobromrnalelinsBare (diose Annaleu Suppl-Bd. 1, 368 und 2 , 91) speter nooh zwei ale Meta-nud ParsbrornmaleZnlure bezeichnete iaomere SRuren al.; Nebenproducte bei der Einwirkung oon Brom auf Bernstcb-sHure erhalten hst (diese Annalan P80, I) ; aber ioh bielt e6 ftlr auisorordentlieb wahracheinlicb , dafs die sogenannto Metabromruale'idure rnit der gewohnlichen Brommde'in&ure und die Parnbrornmale'insliure mit der Isobrommaleinsiinre identisoh &en und glaubte , dab die baobachtetan sehr geringen Voaschiedenheitcn dnrin ihren Orund bXtten, dafa K e k u l d bei seinsn ersten Voreuohen diotie 60 sehr leicht loslichen und deshalb sehr schmar yon kleinen Beimsngmgen eu befreienden Verbinduugen nicht in absoht reinern Zustmde unter Handen gehabt habe. 0,1994 Cirm. gaben 0,1873 AgBr und 0,0021 metallii3chea kg. Berechnet fur C4HSBr04 Gefunaen Es kann keinem Zweifel unterliegen, dafs diese Saure sowohl mit der Bromrnaleinsaure wie mit der sogenannten Metabrommaleinsaure von K e k u 1 B identisch ist. Sie besitzt alle von der fetzteren Siiure angegebenen Eigenschaften und da sie durch Erhitzen der Dibrombernsteinsaure mit Wasser entsteht, mufs sie nothwendiger Weise bei der Darstellung der Br 41,02 40,77. P 6 t r i, weitere Beitrage zur Kenatnifs saiure. Es folgt hieraus, daB eine wirkliche Verschiedenheit zwischen der Isound Parabronimaleinsiiure nicht vorhanden sein kann, dafs vielrnehr die von K e k u 1 B zuerst dargestellte Saure nicht vollstiindig rein war und wahrscheinlich, wie die von mir auf die gleiche Weise bereitete Saure, noch etwas unzersetzte Isodibrombernstt?insaure enthielt. Darauf deutet auch der von Kekuik zu hoch gefundene Brorngelialt. Uebrigens ist auch die Bildungsweise der Isound Parabrommaleinsluren die gleiche, dean man weifs aus den Versuchen YOR F r a n c h i n i o n t *) und B o u r g o i n +*), dafs bei der Einwirkung von Brom auf Beriisteinsaure bei Gegenwart von Wasser auch eine gewisse Menge von Isodihroinberrisleinsaure entsteht und diese mufs sich unter den obwaltenden Verhaltnisseir noth wendig, wenigs&ens theilwaise, weiter aersetzen. Es existiren dernnach nur zwei isomere Siiuren C4H3Br0*. Einwirkung von Wasserstof im Entstehungszustand auf Bromund Isobrommalefnsaure.-Urn einen directen Beweis fiir msere Ansicht zu erhalten, dafs nur die B...
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